Quaternary ammonium alkylamino-benzoquinones



QUATERNARY AMMONIUM ALKYLAMINO- BENZOQUINONES Chester J. Cavallito, Decatur, 111., assignor to Sterling Drug Inc., New York, N. Y., a corporation of Delaware No Drawing. Application December 21, 1955 Serial No. 554,396

15 Claims. (c1. zen-294.7)

This invention relates to quaternary ammonium salts of (tertiary amino)alkylamino-p-benzoquinones, and to processes for their production. 7

This application is a continuation-in-part of my copending application Serial No. 119,760, filed October 5, 1949, now abandoned.

I have discovered that compounds having valuable properties as highly active curarimimetic agents can be obtained by quaternizing (tertiary amino)alkylamino-pquinones obtained from the interaction of p-benzoquinones with (tertiary amino)alkylamines. 7

My invention comprises: interacting a p-benzoquinone with one or two molecular equivalents of a primary or secondary N-[(tertiary amino)alkyl]amine under conditions of mild oxidation to yield, respectively, a 2-monoor a 2,5-bis-[N-(tertiary amino)alkylaminol-p-benzoquinone; and converting the reaction product thus obtained to a quaternary ammonium salt thereof. In those instances where the p-benzoquinone is a tetrahalo-p-benzoquinone, the conditions of mild oxidation are unnecessary for the reaction with the alkylenediamine.

Broadly speaking, the new quaternary ammonium com- 7 pounds provided by my invention have the general formulas and mino radicals, and di(lower alkyl)amino radicals; X and X are hydrogen or a middle halogen, i. e. chlorine or bromine; and An is a non-toxic anion. The iminoalkyl (quaternary ammonium) radicals and Q and Q can be 60 the same or difierent, as desired. Thus, all of my new quaternary compounds contain the parent structure which can be represented by NR-Y (tart) where R is hydrogen or methyl and Y is a lower alkylene atom bridge, or can be considered as derived therefrom by appropriate introduction of the above specified substituents zyl radicals.

Patented July 22,1958

in one or more of the 3, 5, and 6 positions of the parent structure, such substituents including particularly a second iminoalkyl (quaternary ammonium) radical in the 5-position identical with the substituent in the 2-position.

Represented ionically, these quaternary ammonium compounds have the structures The quaternary ammonium grouping, [-N(tert)]+,

makes its chief contribution to the physiological activity 3 of my new compounds by virtue of theelectrostatic field set up at the site of the quaternary nitrogen. Since this contribution is inherent in the quaternary ammonium grouping, the structure of the tertiary amine radical N(tert) can be varied very widely. Thus, this radical can be either cyclic or acyclic in structure and the groups at- "1 tached to the nitrogen can be chosen froma great number of hydrocarbon or substituted hydrocarbon radicals.

For practical reasons, however, I prefer to limit the scope of the radical N(tert) to those cyclic and acylic tertiary amine radicals containing not more than 20 carbon atoms. Moreover, from this restrictedgroup of radicals, I prefer to exclude aromatic amine radicals which j have an aryl radical attached directly to the amino nitro- 1 gen atom, since the low basicity of the arylamines-leads to preparative difliculties and resultant lowered yields of products.

The iminoalkyl-(quaternary ammonium) radicals Q and Q can be represented in a preferred scope by the structural formulations respectively, where R is an aliphatic or arallcyl radical; R R3, R and R when taken separately, represent monovalent organic radicals other than aryl radicals and The aliphatic or aralkyl radicals represented by R are, for example, alkyl radicals, alkenyl radicals, and ben- The preferred radicals of this type are lower alkyl andlower alkenyl radicals containing 1-7 carbon atoms, such as methyl, ethyl, n-butyl, n-heptyl, allyl, methallyl, etc. and (monocyclicfl aryl)methyl radicals, i. e. benzyl radicals, containing 7-10 carbon atoms, and which may carry inert substituents on the ring such as lower alkyl, lower alkoxy, or halogen, e. g, benzyl,.2,4,6-

trimethoxybenzyl, p methoxybenzyl, p chlorobenzyl, I

methylbenzyl, etc.

The monovalent radicals represented byR R R and R include lower alkyl radicals such as methyl, ethyl,

3 n-propyl, isopropyl, n-butyl, isohexyl, etc. and lower alkenyl radicals such as allyl, methallyl, etc.

When R and R or R and R are taken together with the nitrogen atom to form a saturated 5-6 membered heterocyclic ring, the quaternary ammonium radical R1R2Ra -N'R1Rr a I or I An An and' 7 An OHr-CH: (c) Quaternary 'pyrrolidinium radidjals, for example i n CHr-CH! An CHr-CHz and (d) Quaternarythiamorpholinium radicals, for example R1 CHE-'OHI at An GHQ-CH1 It will be appreciated that the unattached valence bond onthe nitrogen represented in the structures for the above radicals is, inthe formula for a complete molecule, attached to one; of the valence bonds of the divalent alkylene radical-Y or Y The divalent lower alkyle'ne bridges represented by the groups'Y and Y in my compounds interpose 2-5 carbon atoms between the two nitrogen atoms connected by the bridge and include alpha, omega-alkylene radicals such as 1,2-ethylene,. CH CH 1.3-propylene 1,4-butylene -CI -I --CH -CH CH and 1,5-amylene --CH CH -CH Radicals of the foregoing type wherein one or more carbon atoms of the bridge hear one or more methyl or ethyl groups as substituents, as represented for example by the 1,2-propylene radical, -CH(CHg)CH also fall within the scope of my invention. The groups Y and Y preferably contain a total of 2-7 carbon atoms each.

In itspreferred scope; therefore, my invention relates to new quaternary ammonium compounds having the where Z is a member of the class consisting of'hydro'gen, lower alkylamino radicals, and di-(lower alkyl)amino radicals; R and R are members of the class consisting of hydrogen and methyl; R is a' member of the class consisting o'f benzyl-radical's containing 7-10' carbon atoms,

lower alkyl radicals, and lower alkenyl radicals; Y and Y are each a lower alkylene bridge inter-posing 25 carbon atoms between the two nitrogen atoms connected by the bridge; N=B and N=B which are identical with, and alternatively designated by, the symbols NR R and NR R respectively, are members of the class consisting of l-piperidyl, 4-morpholinyl, 4-thiamorpholinyl, l-pyrrolidyl, and di-(lower alkyl) amino radicals; X and X are identical members of the class consisting of hydrogen, chlorine, and bromine; and An is a non-toxic anion.

The novel quaternary ammonium compounds of my invention are useful as curarimimetic agents. They are formulated for parenteral use in the manner employed with known curarimimetic or neuromuscular blocking agents such as tubocurarine chloride. Thus, for example they are usually formulated in aqueous solution containing a few milligrams, for instance 2-3 mg., of the compound per ml. of solution. A particularly preferred species of my invention is 2,5-bis-(3-diethylaminopropylamino)p-benzoquinone bis-(benzyl chloride) disclosed in Example 1B below; a representative formulation'of this compound is an aqueous solution containing'3 mg. of'the compound per ml. and, when used intravenously as a skeletal muscle relaxant during surgical procedures in man, an initial dose of- 6-15 mg. (2-5 ml. of the solution) is employed.

The preparation of my new quaternary compounds is conveniently carried out in many instances by direct quaternization of the appropriate N-[(tertiary amino) alkyl]aminop-benzoquinones. Thus, for example, p-benzoquinones containing the (tertiary amino)alkylamino grouping -NRYNR R attached to the 2-position, or 2- and S-positions, of the p-b'enZoquinone nucleus are quaternized by treatment with an alkyla'ting agent which is an ester of an aliphatic or araliphatic alcohol having the formula R OH with 'astrong organic or inorganic acid, said ester having the formula R An where An is" the non-toxic anion of the strong organic orinorg'anic' acid. A preferred group of these alkyl'ating' a ents comprises esters of primary aliphatic and araliphatic alcohols with strong organic 'or inorganic acids. These agents include for example, methyl iodide, methyl bromide, methyl ptoluenesulfonate, dimethyl sulfate, ethyl iodide, ethyl ptoluenesulfonate, ethyl chloroacetate, n-propyl iodide, allyl chloride, allyl bromide, n-hexyl bromide, benzyl chloride, benzyl bromide, p-methoxybenzyl chloride, pchlorobenzyl chloride, etc. The esters of methyl, ethyl, allyl, and benzyl alcohols are especially useful. The general quaterniz'ation reaction proceeds according to the It will be appreciated that when bis-quaternary ammonium compounds are to be formed, the original amine employed for obtaining the above starting material has the formula and the two moles of the ester, R An which are required for the complete quaternization reaction can be added more conveniently in a single step. The quaternization of the amines is simply and conveniently carried out by mixing the selected amine with-one-or two molecular equivalents of the ester; Il -A11 as required,

plus an excess of the ester if desired. The reaction of the ester with the amine can be facilitated by heating the reaction mixture. This is especially advantageous when employing an araliphatic ester such as benzyl chloride as the quaternizing agent, but may be unnecessary or undesirable, for example, in the case of a low-boiling lower alkyl ester where the reaction proceeds with sufficient rapidity at room temperature.

In those instances where the anion, An, in my new compounds is derived from a relatively weak acid such as citric acid or tartaric acid, the direct addition of the ester R An to the tertiary amine does not readily occur due to the properties of the particular ester employed. In such cases it is possible by use of metathetical reactions to replace the anion An of one quaternary ammonium salt by a different anion An without reconversion to the tertiary amine. This is usually effected by treatment of an aqueous solution of the quaternary ammonium salt containing the anion An with silver oxide (hydroxide). The silver salt AgAn is precipitated, leaving in solution the quaternary ammonium hydroxide. It is prerequisite, of course, that the salt AgAn be insoluble in water. The quaternary ammonium hydroxide may then be neutralized with the appropriate acid H--An, which can be either a strong or a weak organic or inorganic acid, to give any desired salt with a pharmaceutically acceptable anion.

The starting amines required for the above quaternization procedures can be prepared conveniently by the following procedures. When X and X are hydrogen those amines having one (tertiary amino)alkylamino group,

NR-YNR R are obtained by interacting a p-benzoquinone having the formula l r-Y-nma When Z is hydrogen, a second (tertiary amino) alkylamino group can be introduced readily into the 5-position of the 2-[(tertiary amino)alkylaminol-p-benzoquinone by causing a second molecular equivalent of the alkylenediamine,

NH(R)YNR R to react, yielding a symmetrical com- On the other hand, when thesecond equivalent of alkylenediamine is structurally difierent from the first, an unsymmetrical disubstituted' product is obtained, as represented by the following equation:

The 2-[(tertiary aminojalkylamino]-p-benzoquinones also react with primary and secondary alkylamines under conditions of mild oxidation to introduce a S-alkylamino or S-dialkylamino group, respectively, into the p-benzoquinone nucleus, as illustrated by the following equation:

where R is a lower alkyl radical containing 1-7 carbon atoms and R is hydrogen or a lower alkyl radical containing 1-7 carbon atoms. In the preparation of 2- [(tertiary amino)alkylamino] 5 (monoor di-alkyl)- If it is desired that the (tertiary amino)alkylamino groups introduced at positions 2 and 5 of the p-benzoquinone nucleus as above-described be identical, the reaction can be carried out either in one operation by re acting p-benzoquinone with two molecular equivalents of the alkylenediamine or, less conveniently, in two steps,

introducing first I one (tertiary amino)alkylamino group and then the other: whenp 'on the other-hand, it is desired 'tointroduee' ditferent (tertiary amino)alkylamino groups at positions 2 and SJ-the -reac'tion'must'of course can be carried out in concentrated solution so that the 2-(tertiary a'minoalkylamino) p benzoquinone precipitates from thereaetion medium as it is formed, in which case a considerable excess of the alkylenediamine can be employed to increasethespeed of reaction without the disadvantage'of producing an appreciable quantity of the 2,5 bis-(tertiary aminoalkylamino)-p-benzoquinone when the his compound is an undesired by-product.

Instead of employing p-benzoquinone as such, hydroquinon'e can be employed as the starting material, the hydroquinonebeing converted by the oxidizing atmosphere (furnished, for example, by use of a mild oxidizing agent such as hydrogen peroxide, oxygen, air, a quinone, etc.) of the reaction mixture to p-benzoquinone. However, when hydroquinone is employed, the reaction time required is increased, and therefore I prefer to use pbenzoquinone itself.

The use of oxygen in maintaining the oxidizing atmosphere in the reaction mixture is generally tobe preferred over use of air, since the reaction proceeds more rapidly when oxygen is employed. However, the use of air ofiers a useful alternative when oxygen is not available. In the preparation of mono-(tertiary amino)alkylamino-p-benzoquin'one's, it is convenient to employ an excess of the p-benzoquinone amounting to about one molecular equivalent or more in the reaction to function as a mild oxidizing agent, in which case the use of gaseous oxygen or air is not necessary. This procedure has the added advantage that the reaction time required is usually only about one-half to one hour, while when oxygen or air is used as the oxidizing, agent the reaction' time is usually at least severalhours. The interaction of the p-benzoquinone with the alkylenediamine is advantageously carried out in asolvent, the choice of which can be made frorna wide variety of organic solvents. acetonitrile, and benzene, for example, are excellent solvents for use in my process and are somewhat more satisfactory in-this' regard than are water and alcohol.

The preparation of the starting amines having the formula

where X is a middle halogen (chlorine or bromine) is effected by interacting chloranil or bromanil, respectively, with the appropriate alkylenediamine, two molecular equivalents of alkylenediamine being employed. The re- I' have found that dioxane,

action proceeds by spiittingsout hydrogen halide,,and-

oxidizing conditions are not..:required. The reaction .pro-

ceeds according to the followingequationwhen forex ample'a'symmetrical biscompound is desired:

My invention is illustrated by the following examples without, however, being limited thereto. These quaternary ammonium compounds have high curarimimetic activity; when aqueous solutions were assayed in mice.

by a modification of-the inclined screen procedure used by Thompson [Endocrinology, 39, 62 (1946)] for determination-of insulin, the compounds showed a general range of ED (efiective dose producing paralysis in 50% of the mice) values from 0.2to 33 mg./kg. with most of the ED values being onthe order of 0.3-0.9 ing/kg. The L'D (dose causing death by subcutaneous injection in 50% of the mice) values as estimated by the method of Miller and Tainter [Proc. Soc. Exp. Biol. Med, 57, 261 (1944)] ranged from 0.6 to mg./kg. with most of the LD values being on the order of 0.6-4 mg. /kg. The ED and LD values for 2,5-bis-(3-diethylaminopropylamino)-p-benzoquinone bis-(benzyl chloride), de-

scribed for instance in Example 1B, were 0.8 mg./kg. and 2.5 mg./kg., respectively.

EXAMPLE 1 A. 2,5-bis- (3-diethylaminopropylamino) -p-benzoquinone 104 g. of N,N-diethyl-1,3-propanediamine was added to 44 g. benzoquinone in 500 ml. of dioxane, with provision for external, cooling of the reaction mixture when necessary. Oxygen was bubbled through the solution for approximately 20 hours. The reaction mixture was then cooled in an ice-bath. A red crystalline precipitate formed and this was filtered oil? and recrystallized from hot ethanol. There was thus obtained, as a red crystalline compound, 35 g. of2,5-bis-(3-diethylaminopropylamino)- p-benzoquinone which meltedat-122-124" C. A small additional crop of this product was obtained by concentration of the dioxane mother liquor.

Analysis.-Calculated: N, 15.37%; C, 65.89%; H, 9.96%. Found: N, 15.18%; C, 65.91%; H, 9.68%. The compound formed a dihydrochloride which was obtained as a red powder which melted at 250-25 1 C. (dec.).

bis-(benzyl chloride) l GE's-C6 5 35 g. of 2,5-bis-(B-diethylaminopropylamino)-p-benzowith 2,-bis' (3=ethylrnethylaminopropyliauninj ti-berino quinone was dissolved in 500 ml. of 95% ethanol, and quinone; v 60 g. of benzyl chloride was added to the solution. The I p o mixture was refluxed for four hours and was then cooled. OH; An equal volume of ether was added to the reaction mix- 5 NflwnrcHronrN/ ture, thus precipitating a red oil which crystallized on OH; standing. The precipitate was collected on a filter, and \LCHrCHrCHPNH re-precipitated with ether from solution in 95 ethanol twice more. The product was dried in an oven at 80 C.

' ere was thus obtained 51 g. of 2,5-bis-(3-diethylaminopropylamino)-p-benzoquinone bis-(benzyl chloride) as an which is obtained by interaction of N-ethyl-N-methylorange-red solid which melted at 191-195 C. The melt- 1,3-propanediamine and p-benzoquinone in the presence ing point varied somewhat with the rate of heating. The of oxygen by a procedure similar to that described in compound was highly water-soluble. Part A above. t I

Analysis.-Calculated: N, 9.08%;C1, 11.48%. Found: Thecompounds described belowlin the following parts N, 9.28%; Cl, 11.68%. v E -P, inclusive, of this example were obtained by inter acting 2,5 -bis- (3-diethylam'inopropylamino) -p-benzoqui- C. 2,5-bis-(3-diethflmninopropylamino)-p-benzoquinone none Wlth two eqPivalents thefilfpropriate a1k1ating bi3. meth0bmmide agent under reaction condition similar to those in the quaternization procedures described hereinabove.

A solution of 5 g. of 2,5-bis-(3-diethylaminopropylamino)-p-'benzoquinone in 100 ml. of ethanol was mixed at about 25 C. with. methyl bromide. After the mixture 7 had stood for about 2 hours, a precipitate formed (in an- ''M. P. 231-235 C. Solubility in water, weight/volume, other run, the precipitate formed after addition of ether less than 0.25%. Solubility in 95 ethanol, weight/volto the reaction mixture). The precipitate was collected, ume, less than 1%.

F. 2,5-bis-(3-dielhylwminopropylamino)-p-benz0quinonebis-propobromide onFcm-on, cm-orn-crr,

NH-CHl-CHl-OHP B 0 Hz N-CHg-CHFCHpNH r washed with dioxane, and dried in an oven at 80 C. M. P. 223-225 C. Solubilityinwater, weight/volume There was thus obtained 7.7 g. of 2,5-bis-(3-diethylgreater than 20%; pH of 1% aqueous solution was 5.7.

' G. 2,5-bis-(3-diethylaminopropylamino)-p-benz0quinone bis-butobromide i A CHr-CHs-CHz-CH:

onr-cm-om-cn.

C2Hr

-cH,-oH,-cm-Nn r 06in aminopropylamino)-p-benzoquinone bis-methobromide M.- P. 209-212 C. Solubility in water, weight/volume,

(which is alternatively named as 2,5-bis-(3-ethylmethylgreater than 20%; pH- of 1% aqueous solution was 7.2. aminopropylamino)-p-benzoquinone bis-ethobromide) as an orange powder which melted at 225 C. p H. 2,5-bis (3-diethylaminopropylamina)-p-benzoquinone Analysis.-Ca1culated: N, 10.10%; Br, 28.82%.- bis-ethobromide Found: N, 10.38%; Br, 28.95%. 0 C When the quaternization was repeated using a 1:1 mix- I 01m 01H: ture of ethanol and dioxane as the solvent, the desired p NEofiroflroHrN bis-methobromide was obtained in substantially the same 1 01 p r B1 CzHs. y N-OHz-OHs-OHz-NH V D. Alternatively, the bis-methobromide described in Part C above is prepared by interacting ethyl bromide 2344 15851.: 1 1., M-iB. 2404M? C. Solubi1ity in water,=weight/vo1ume-.+ greater than 20%; pH of 1% aqueous solution was;

I. 2,5-bis-(3-die1hylaminopropylamino)-p-benzoquinone bis -(allylv bromide) M. P. 222' C. Solubility in water, weightlvolumw greater than 20%;:pHof 1% aqueoussolution-was-5.2.

M. P. 198-200 C. Hygroscopio, solub l min wa 7 ter, weight/volume, greater than 20%; pH of 1% aque: ous solution was 7.0.

K. 2,5 bis (3-diethylaminopropylamina )-p-benz0quihorig; b -(n-M robe z 1h 0ri 1 M. P. 204-205" C. (dec.). Solubility in ater, Weight/volume, 2.5%; pH of 1% aqueous solution was 5.0. Y

L. 2,5-bis(3-diethylaminopropylamino)-p-benzoquinone bis- (och l orobenzyl-chloride) M. P. 117-140 C. Very hygroscopic. Solubility in water, weight/volume, greater than 20%; pH of 1% aqueous solution was 6.5.

Mr S- -d t a nmz o amin lrpenzpq m 1.

bis-(o-methoxybenzyl chloride)-, V

0 CE: C135 NE-CH GHrGHPN CaHi 1 cm;

GHrGH-;GHa-NH W 2,844,586 U 13 141. M. P. l82-184 C. Solubility in water,weight/volume, for twenty hours. The reaction mixture was content -greater than 20%; pH of 1% aqueous solution was 8.7. trated and the solid product which separated was col N. 2,5-bis-(3-dz'ethylaminopropylamino)-p-benzoquinone bis-(2,3-dimethoxybenzyl chloride) M. P. 148-l 56 C. Very hygroscopic. Solubility in lected. and recrystallized from hot aqueous ethanol. water, weight/volume, greater than 20%; pH of 1% There was thus obtained 54 g. of 2-(2-diethylaminoethylaqueous solution was 4.5.- k V amino)-p-benzoquinone in the form of orange crystals 0. 2,5-bis-(3-diethylaminapfopylamina)-p-benzoquimme bis-(p-nitrobenzyl chloride) I QHONO.

NH-CH -OH -CHr-N CIH:

CaHl GHgOHz-CH:NH 1 t 0.11. 1

M. P. 195-197.5 C. Solubility in water, weight/volwhich melted at 119 C. ume, less than 0.25%. Solubility in 95% ethanol, Analysis-Calculated: N,' 12.60%. Found: N, weight/volume, less than 1%. 12.51%. I I I P. 2,5-bis-(3-diethylaminoprapylamino)-p-benzoquinon bis-(m-nitrabenzyl chloride) N0, oral-G I M. P. 190-203 C. Solubilityinwater, weight/volume, B. Quaternary salts of Z-(Z-diethylamiiwethylamino)- greater than pH of 1% aqueous solution was 7.6. p-benzoquinone v y 2-(2-diethylaminoethylamino)-p-benzoquinone was re- EXAMPLE; 2 1 acted with one molecular equivalent of methyl bromide 2 (idimethylaminoethylamina) p benzoquinone to yield 2-(2-d1ethy1am1noethylam1no)-p-benzoquinone 5 methobromide,

I I 0 H H Nn-cm-om-Nwmm C? NH-cHr-oH r I 01H! To a: solutionof- 54 g. of p-benzoquinone in 500 m1. 7 1 of dioxane there was added g. of N,N-diethylethwhich had an indefinite melting point and decomposed ylenediamine, and oxygen was passed into the solution .5 when heated above 225 C. 4

15 Analysis..Calculated: N, =8.84% Found: .N, 9.28%..

Alternatively, this compoundis prepared. .by interacting equivalent amounts of ethyl bromide and 2-(2-ethylmethlyaminoethylamino)-p-benzoquinone, the tertiary amine reactant being obtained by interaction of one molecular equivalent of N-ethyl-N-methylethylenediamine and p benzoquinone in the presence of oxygen,

The amine reacts with one molecular equivalent of methyl sulfate to yield Z-(Z-diethylaminoethylamino)- benzoquinone methosulfate.

(1) 115 g. of N,N-diethylethylenediamine was added to a solution of 54 g. of p-benzoquinone in 500 of dioxane and the mixture was heated on a steam bath for about twenty hours, during which period oxygen was bubbled through the solution. The reaction mixture was then concentrated at reduced pressure. The resulting residue was recrystallized from hot aqueous ethanol.

There was thus obtained 40 g. of 2,5-bis-(2-diethylamino ethylamino)-p-benzoquinone, which melted at 134135 C.

Analysis. C alculated:..N, 16.65%} C,,f64.20 H, 9.58%. Found: N, 16.65%; C, 64.21%; H;9.40%.

(2) When 42 g. of 2-(2-diethylaminoethylamino)-p-' benzoquinone Was reacted with 61.5 g. of N,N-diethylethylenediamine under conditions similar to those de v,

scribed in part (1) above, there was obtained 31 g. of

CLIPS-OCH; i mm NH-OHr-CHi-N 02H. 02H:

N-"CHr-GHf-NH cam- EXAMPLE 4 A. 2,5-bis-[2-(4-morpholinyl)ethylaminol-p-benzoquii GHQ-0H5 xn omom-N o ism-c o -CHr-CH=NH CH'r-C l 16 in Example 11B; There. .was 'thus obtained 4.5 g. of 2,5-

bis (25- diethylaminoethylamino) -;.p benzoquinone.

bis-(benzyl chloride),

CHa-CeHs Cz a 1 G2Hs N-CHa-CHr-NH a highly water-soluble solid with an indefinite melting point, ca. -165180 C.

Analysis.--Calculated: N, 9.50%; CI, 12.02%; Found: N, 9.49%; Cl, 12.36%?

Two molecular equivalents of n-propyl bromide react with the amine to yield 2,5-bis-(2-diethylaminoethylamino)-p-benzoquinone bis-(n-propyl bromide),

Two molecular equivalents of allyl bromide reacted with the amine to yield 2,5-bis-(Z-diethylaminoethyiamino) -p-benzoquinone bis-(allyl bromide), I t

which meltedat 233 23416..

By interaction of the 2,5jbisf(Z diethylaminoethylf amino)-.p-benzoquinone with two molecular equivalents of p-methylmercaptobenzyl bromide there is produced @5: #(2- th laminasth laminql: -benzoq i a (plmers qbsnz lbmmid li oHrOs-om To a solution of 10.8. g. of p@benzoquin one. in 250 ml. of dioxane there was added 29 g. of 4-(2-ajminoethyl) morpholine and oxygen was bubbled into the solution for about fifty hours. The reaction mixture was then cooled and the crystalline precipitate which was present was collected ona filter and recrystallized from a hot ethanoldioxane mixture to yield g; of 2, bis-[2-( 4- morpholinyl)ethylamin ]-p-benzoquinone as orange-crysn15, when melted at 189-190 C.'-

. 17 Analysis.--Calcu1ated: N, 15.38%; C, 59.32%; H, 7.74%. Found: N; 15.38%; C, 59.31%; H, 7.82%. B. Quaternary salts of 2,5-bis-[2*(4-morpholinyl)ethylaminol-p-benzoquinone 2,5-bis-[2-(4-morpholiny1)ethylaminol-p-benzoquinone was reacted with methyl bromide by a procedure similar By interaction of 2,5-bis-[2 (4-thiamorpholinynethyl- 5 amino]-p-benzoquinone with two molecular equivalents of methyl bromide there is obtained .,2,5-bis-[2 (4- thiamorpholinyl)ethylaminol-p-benzoquinone bis-methoto that described in Example 1C, and there was thus "bromide, v

i 1T cm-on; NH-CHz-bHr-b/ V s /CH2 'GH2 cm v r CHBOQ s GHzOHr-NH \OH:C I Br obtained 2,5-bis-[2-(4-morpholiny1)ethylaminoJ-p-benzoquinone bismethobromide,

When the tertiary ainine is reacted with two moleculer equivalents of benzyl chloride, there is obtained 2,5-biso I cm OHr-CHi N'H- CHr-CHz-N /CHr-C H: C I

which melted at 231-234 C. (dec.).

Analysis.-Ca lculated: N,

Found: N, 9.84%; Br, 28.12%.

The 'amine reacts with two molecular equivalents'of ethyl iodide to yield '2,5-bis-[2-(morpholinyl)ethylaminol-p-benzoquinone bis-ethiodide,

. NH-CHs-CH /CH:CHa em EXAMPLE 5 A. 2,5-bis- [2- (4-thiam0rph0linyl) ethylaminol-p-benzoquinone 10.10%; Br, 28.02%.J

OER-CH! CHr-CQ:

[2-(4-thiamorpholinyl)ethylamino]-p benzoquinone bis- (benzyl chloride), i

' C r-C I NH-CHa-OHr-N s 1 c ne-on,

N-oH cHs- H OKs-CH:

cm-c.

S\ N-CHPCHr-NH CHr-C To a solution of 10.83. of p-benzoquinone in 250 of dioxane there is vadded 32 g. of 4*(2-aminoethyl) thiamorpholine and oxygen is bubbled into the solution for about fifty hours. The reaction mixture is then cooled 70 and the precipitate present is collected on a filter and recrystallized from a hot ethanol-dioxane mixture to obtain 'as an orange-red solid 2,5-bis-[2-i(4-thiamorpholinyl) 'ethylaminol-p-benzoquinone.

*the' solutionfor four"hours. The reaction mixture was then concentrated under reduced pressure and'water was --added to 'the residue. The-so1id which precipitated was collected on .a filter and recrystallized from aqueous i9 20 1104asolution;.of ;5.4.g. of p-benzoquinonein 50 ml. ;B. Quatemary salts 20f;2-tz-diethylaminoethylamino)-5- of dioxane therewas-added 1,0,2 g. of N,N-dimethy1- ;(3-dimethylaminopropyiamino)rp-benzoquinone 1,3 propylenediamme andthe oxygen was bubbled through 12 (2 diethylammoethylamino) J 5 (sidjmethyk 5 amiuopropylamino) -p-.benzoquinone :reacts with two equivalents -of benzyl -bromide.:and with tworeguivalents of ,n-propyl .:ch1orid,e', respectively, .to yield .the hemeethanol. There was obtained in this manner-:6;8;.g. of F e h lh t l? GHa-CoHr 2-(3-dimethylaminopropylamino) p-benzoquinone, which 0 meltedat t59-160" C. 16 I Afialysis. -;-Ca1 culated: N, 13.44%; C, 63.40%; H, NECH CH N "7.74%. Eound:N,*l3i29%;"iC, 63.18%; H, 8.05%. H.

B."Quktternary salts of 2- (3dimethjalamimypropylamina) N-GHrOH2-OH2NH Br p-benzoquinone v c 3 Br 2-(S-dimethylaminopropylamido) -p-benzoquinone reacts with benzyl chloride and with p-chlorobenzyl and the propochloride having the formula 0 om-carom I 01H: CHr-CHr- H:

. NH-OHr-OHP CE: 1 Gig -.ortr-'oH,-oH--Nn chloride to yield, respectively, 2-(3-dimethylaminopropy1- EXAMPLE 8 amino)-p-benzoquinone benzyl chloride, which has the formula U A. 2-[3-(1-piperidyl)propylaminohp-benzoquinone are om CHz-CH: N/ NH-OHr-CHz-CHs-N CH: Cl CH: Clix-C and '2 (3 dimethylaminopropylamino) .p. -j;benzo quinone p-chlorobenzyl chloridegwhich has the formula To a solution of 12 g. p-benzoquinone (excess p-benzo- 40 quinone employed as oxidizing agent) in 100 ml. of di- GIL-O01 oxane there was added 7.5 g. of l-(3-aminopropyl) piperidine and the solution was stirred-for one hour. The

| CH; reaction mixture was then cooled-and the crystals which separated from .solution'were collected on-..a .lilter and recrystallized from .hot .ethanolrdioxane. solution. Ihere was thus obtained 5 g. of 2-[3-(1-piperidyl)propylamin0]- lp-benzoquinone in the:form of red crystals, which melted at1200-201" C. '(dec.). 7 .Analysis.--Calculated: N, 11.29%; C, 67.71%; H, EXAMPLE 7 8.12%. Found: N, 10;91%; c, 67.38%; H,"-8'.'38%. A. 2-(2-diethylamin0ehylamino)-5-*(3-dimethylaminb- The compound formeda hydrochloride which was obpropylamino)-p-benzoquinone tained as a light brown powder which melted at 251- I CHI N -GHr-C r wflm 65 B. Quaternary salts of 2'-['3=r(1-piperidyl)propylamino]- ipabenzoquinvne (C JM -CHrCEr-CHrNH When 2-[ 3-( l-piperidyl) propylamino] -p-benzoquinone 0 was quaternized by treatment with methyl bromide, using To a solution of 25 g. of N,Ndimethyl-1,3-propanea procedure similar to that described in Example 1C, there diamine in 500 ml. of dioxane there is added 42 g. of was obtained '2['3-(1-piperidyl)propylamino]-p-benzo- 2-(2-diethylaminoethylamino) -p-benzoquinone and oxyv quinone methobromide, gen is bubbled through the mixture for four hours. (Prolonged reaction periods favor the formation of the symmetrical bis compounds as by products due to dispro- E CH CH portionation of the desired unsymmetrical bis compound.) The reaction mixture :is hen concentrated under reduced .2 NHf-UHPCHr-GHPN I pressure and. the resulting. residue is collected on a filter r gmand recrystallized from hot aqueous ethanol. There is Y Y thus obtained 2 (2 diethylaminoethylamino) 5 -"(3- g dimethylaminopropylamino.) p-benzoqui none.

Alternatively; the same product is obtained by interacting 2-(3-dimethylaminopropylamino)gp-benzoquinone whichmeltedat 255C. I with N,N-diethylethylenediamine in the presence of Analysis-Calculated: N, 18,1 7 Br, 23.28%. oxygen, y 7 Found: N, 8.13%;Br,23.70%'. w

When 1-(S-aminopropyl)-2-methylpiperidine is employed in part A of the foregoing example, there is obtained as a product 2-[3-(Z-methyl-1-piperidyl)propylaminoJ-p-benzoquinone, which interacts with one molecular equivalent of methyl bromide to produce 2-[3-(2- methyl-1-piperidyl)propylamino]-p-benzoquinone methobromide and with one molecular equivalent of ethyl sulfate to yield 2-[3-(2-methyl-l-piperidyDpropylaminop-benzoquinone ethosulfate. i

EXAMPLE 9 A. 2-[3-(1-pyrrolidyl)pr0pylamino] p benzoquinone and quaternary salts thereof When 7.3 g. of 1-(3-aminopropyl)pyrrolidine was substituted for the 7.5 g. of 1-(3-aminopropyl)piperidine in the procedure described in Part A of Example 6, there was obtained as the product of the reaction 2-[3-(1-pyrrolidyl)propylaminoJ-p-benzoquinone, which has the formula CHr-CH:

NH- -CHPCHr-CHr-N CH:- H:

' and which reacts with benzyl chloride and withallyL chloride to yield, respectively, 2-[3-(l-pyrrolidyDprooatcm pylaminoJ-p-benzoquinone benzyl chloride, which has the formula CHr-CnHs CHE-CH2 NH-OHi-CHz-CHr- 1 CH2GH2 Bl G CHr-CH:

H's-Ca r and 2-[3-(1 pyrrolidybpropylami'no]-p-benzoquinone allyl chloride, which has the formula The amine reacted with one equivalent of methyl bromide to form the methobromide having the formula which sintered'at tion at 239-240 C. .7

By interaction .of the amine with one equivalent of p-acetamidobenzyl bromide there is obtained 2-[3-( l-pyrrolidyl)-propylamino]-p-benzoquinone p-acetamidobenzyl bromide,

CHONHECO-GH$ 0 r I a I (KHz-CH2 I I NH-CHa-OHr-CHr-e C. and melted with' 'decomposi- B. 2,5-bis-[3-(1-pyrrolidyl)propylaminol-p-ber|zoquin0ne and quaternary salts thereof p-Benzoquinone was interacted with two molecular equivalents of l-(3-aminopropyl)pyrrolidine to produce 2,5-bis-[3-(1 pyrrolidyl)propylamino] p benzoquinone, having the formula CHI-CHI NH-CHr-CHr-CHzwhich melted at -156" C. Alternatively, this compound is obtained by interacting 2-[3-(1-pyrro1idyl) propylamino] -p-benzoquinone with one molecular equivalent of 1-(3-aminopropyl)pyrrolidine). The bis-tertiary amine reacts with two equivalents of 3-bromobenzyl bromide to yield the bis-(3-bromobenzyl bromide) having the formula CHz-CH:

.sandrmithtwo molecular equivalents-of -p-prop'oxybenzyl The aniine reacted with one equivalent'of methyl brotained as a pink solid whieh melted at-2'53-25S "C. (dec.). 40

ehloride to yield the-:bis-(papropoxybenzylchloride) havmide to yield '2-[N-3-( l piperidynpropyl- N-methylmg theformula (LO-on CHI-CHI "1 NH-n or! on N mm- 011: r P i N-cHr-cm-cm-NH om-ogdl EXAMPLE aminol-p benzoquinone methobromide,

A. 2-[N- -(3-piperidyl)propyl-N-methylamino]-p-benzoi 1 quinone 2o I l cilia--03: 0 a. .0K; tom-Tom N-CHr-CHa-CH:- cu,- OHPC a GHQ-refit By interaction of the amine with one equivalentof 3- chlor0-4-methoxybenzyl bromide, there is obtained 2- "[N .3-(.1-piperidyl)propyl N-methylamino]-p benzoqui- 0 none I3-.chloro-4'-methoxybenzyl bromide, V

15.6 g. of "l-(3-methylaminopropyl)piperidine was added with cooling to 10.8 g. of p-benzoquinone in 100 ml. of dioxane. Oxygen was then bubbled through the 3 solution for one hour. Thereaction mixture was cooled p and the crystalline solid which separated was 'collected f on a filter and recrystallized :from aqueous ethanol. There O was thus obtained 15.5 g. of 2-[N-3-(1-piperidyl)propyl- 0 N-methylaminol-p-benzoquinone in the form of red plate I V I GHQ-CH1 -Analysis-.:Ca1culated: --N, .I'0L69% 'C, .68i69%.; .H, 8.44%. FoundnN, '1:0.72%;xC,i68:65-% H, 8.67%.

vThis compoundformed a hydrochloride which was 0b- 8 r (am-ed,

A. 2 -"[N -3*(1-piperidyi)propyl-N-methylamirtol-5 (3- V dimethylaminopropylamino)-p-benzoquinone O I OH; CHa-CH:

N-CH2C Hz-CHr- CH1 B. Quaternary salts of 2-[NJ-( 1-piperidyl)propyl-N- 11.2 g. of N,N-dimethyl-l,3-propanediamine is dism-ethylamino] -p-benzoquinone solved in 200 ml. of dioxane and to this solution is added 26.2 g. of 2-[N-3-(l-piperidyl)propyl-N-methylamino]- ex 1 iodide to ield p-benzoqlunonm "Oxygen 1s -then bubbled 'throughfithe 3232;326:823 fig getgylamino] benzoquimfne solution for two hours. The reactronmrxture 1s Iconcentrated and cooled and the solid whlchseparates from n solutlon 1s collected on a filter. There 15 thus obtained 2 [N 3 -(1 piperidyDpropyl N methylamino] 5- (3-dimethylaminopropylamino-p benzoquinone. B. Quaternary salts of 2-[N-3-(I-piperidybpropyl-N- 'N-C-H,C'Hr--GH;N 0H1 methylamino] 5 (3 dimerhylamz'nopropylamino)-pbenzoquinone 2 [N-3-(l-piperidyl)propyl-N-methylamino] -p-benzo- CHr-CH: I

The tertiary amine prepared as described above reacts with two molecular equivalents of methallyl bromide to yield the bis-(methallyl bromide) having the formula CH: CHz-(i =C CH: 0 (g I CH: CHI-CH! CH1= CH:

N-CHg-CH -GH CH, CH: g

I. CHr-C g 25 equivalents of p-fluorobenzyl bis-(p-fluorobenzyl bromide) havand two molecular bromide to yield the ing the'formula 26 6.03%.- Found: N, 9.38%; Cl, 11.87%; H O (Karl Fischer method), 5.49% p 4 Two equivalents of methyl iodide react with .the amine Gag.

FOUR, on. ,p i 0:11-03,

I C r-' H r-' H:N CH: 1' GHQ-C65 -CHsCH:CHs-NH EXAMPLE-12' 15 to yield 2,5-bis-g3-dimethylaminopropylamino)-p-benzo'- A. 2,5 bis- (3 -'dimethyldminopropylamind) -p benzo- 3m f f fl CH8 quinone" 0 i I CH:

H- H 0 on I OH: CH, N C Hr- Nn-onrcm-om-Nwm) (C OIN-CHr-CHa-OHrNH 10.2 g. of N,N-dimethyl-1,3-propanediamine was added to 5.4 g. of p-benzoquinone in 100 m1. of dioxane and oxygen was bubbled through the solution for about thirty hours. The reaction mixture was then'concentrated under reduced pressure and the residue thusobtained was stirred with ethanol and water. There was thus obtained from the mixture, as an insoluble product,

3 g. of 2,5-bis-(3-dimethylaminopropylamino) -p-benzoquinone in the form of red crystals which after washing with ether melted at 125-l26 C. Analysis-Calculated: N, 18.17%; C, 62.35%, H, 9.15%. Found: N, 17.65%; C, 61.85%; H, 9.16%.

OKs-BOOGIE:

A. 2,5- bis- 3 u- CH3 NH-CHa-CHr-CHr- EXAMPL E13 n propylaminaprapylaminq) p be r goquinone n-mm N-om-oHr-orn-NH B. Quaternary salts of 2,5-bis-(3-dimethylaminopropylamino)-p-benzoquinone Using a procedure similar to that described in Example 1B, 2,5-bis-(S-dimethylaminopropylamino)-p-benzoquinone was heated with an' ethanolic solution of benzyl chloride, thus yielding 2,5-bis-(3-dimethylaminopropylamino)-p-benzoqu inone bis-(benzyl chloride) as the dihydrate,

0 0112-0111:: CE CH: 0 NH-QHrOHg-OHz-N .21110 Pen, N-OHrCHa-CHa-NH p I C 3 l which had an indefinite melting point, ca. 205-225 C. Analysis.Calculated: N," 9.38%; Cl,-1l.'87%; H 0,

To a solution of 8.1 g. of p-benzoquinone in 150 ml. of dioxane there was added 23.7 g. of N,N-di-n-propyl- 1,3-propanediamine, and oxygen was bubbled through the solution for forty hours. The reaction mixture was concentrated under reduced pressure and the residue was dilutedwith water. An oil which later solidified separated from the aqueous layer. This solid product was crystallized fi-om hot petroleum ether. There was thus obtained 14.5 g. of 2,5 bis-(3-di-n-propylaminopropylamino)-p-benzoquinone in the form of red crystals which melted at 65-66 C.

Analysis-Calculated: N, 13.34%. Found: N, 13.52%.

'- B. Quaternary was of 2,5 bis (3 di n proplywminopropylamino) -p-benz0quinone 2,5 bis (3 di n propylaminopropylamino) p benzoquinone 'was quaternized :by treatment with two 30 EXAMPLE 15 1 A. 2,5 bis" IN 4 3 (1 pipefidyDpropyl-N-methylaminol-p-benzoquinone 0 I EH: N/OHPGEI Ont CH, CH -CHr-CHr-CH: CH:

111 GE's-C CH: O lCH:CHI

15.6 g. of l-(3-methy1aminopropyl)piperidine was added with cooling to a solution of 5.4 g. of p-benzo- The amine reacts with two et uivalents of p-methoxybenzyl chloride to yield 2,5-bis-[N-3-(1-piperidyl)propylquinone in 150 ml. of dioxane and oxygen was then 15 N-methylarninol-p-benzoquinone bis-(p methoxybenzyl bubbled through the warm solution for twenty hours.

omoOoH, /CHz-CH: cm

CHr-CHI The reaction mixture was concentrated under reduced chloride) EXAMPLE 16 A. 2,5-bis [3- (4-m0rph0l inyl) propylaminol -pbenzoquinone GET-CH2 N H-GHz-OHz-CHr-N /0 CHr-CH:

To a solution of 10.8 g. of p-benzoquinone in 75 m1.

pressure. The concentrated mixture was cooled, and the 40 of dioxane there was added 14.4 g. of 4-(3-aminopropyl)- red crystals which separated were collected and recrys tallized from aqueous ethanol. There was thus obtained 8.2 g. of 2,5 bis [N-3-(l-piperidyl)-propyl-N-methy1- aminol p-benzoquinone, which melted at 117-118 C.

Analysis.Calculated: N, 13.47%; C, 69.19%; H, 9.68%. Found: N, 13.75%; C, 69.48%; H, 9.74%. B. Quaternary salts of 2,5-bis-[N-3-(I-piperidyDpropyl- N-methylamino]-p-benz0quinone 5 g. of 2,5 bis [N 3-(1-piperidyl)propyl-N-methylaminol-p-benzoquinone was quateruized by treatment with methyl bromide to yield 5.4 g. of 2,5-bis-[N-3-(1- piperidyl) propyl N methylaminol-p-benzoquinone bismethobromide,

morpholine, and oxygen was bubbled through the solution for 10 hours. The reaction mixture was cooled and the orange-red crystals which separated were collected on a filter and recrystallized from hot ethanol. There was thus obtained 8 g. of 2,5-bis-[3-(4-morpholinyD- propylamino]-p-benzoquinone, which melted at 200 C. Analysis.-Calculated: N, 14.28%; C, 61.19%; H, 8.22%. Found: N, 14.16%; C, 60.98%; H, 8.50%.

' B. Quaternary salts of 2,5-bis-[3-(4-morph0linyl)- propylamino]-p-benz0quinone 2,5-bis-i3-(4-morpholinyljpropylamino] p benzoquinone was quaternized by treatment with methyl browhich melted at 245-250" C. (dec.).

Analysis-Calculated: N, 9.25%; Br, 26.39%.

Found: N, 8.71%; Br, 25.95%.

which melted at 248 C. (dec.).

31 32 Analysis.-Calculated: N, 9.63%;Br, 27.47%. Found: By interaction'bf theamine with one equivalent of N, 9.33%; Br, 27.20%. 1 2,4,5-trichlo-robenzyl chloride, thereis obtained 2-(4-di- The amine reacts with two equivalents of benzyl chlo ride to yield 2,5-bis-[3-(4-morpho1inyl)propylamino]-pbenzoquinone bis-(benzyl chloride), 7

o ore-cam cm CH CHr-CH:

P Na-cm-om-om-N 0 GHr-CH: C1 CHr-C 2 0 GHI-CH2GHP'NH cm-cia i "1 EXAMPLE 17 i y o y m p-benzoquinene -2,4,5' &ii11om. benzyl chloride, 7 Z UI-Iiiethylqminobutylamino)-p-benz0quin0ne 20 G1 0 I on 01 1 To 8.7 g. of p-benzoquinone inro'omil. of dioxane EXAMPLE 18 there was added 23 g. (one equivalent plus anexcess) I A. 2-(4-diethylaminobutylamino)-5-methylamino-pof N,N-diethyl-1,4-butanetliarriine and. ox gen was passed benzoquinone into the reaction mixture for about tweiity'hours. There 0 was obtained a crystalline precipitate which was collected on a filter. The mother liquors were concentrated to yield a secondcropof the product. The combined crops I of product were recrystallized from {an ethanol-water V GHPNH mixture. There was obtained in this maflher"8.8'g.of 2(4- diethylaminobutylamino)-p-benzoquinone, which melted at 123-125 C.

- 40 3 g. of 2-(4-d1ethylammobutylammo)-p-benzoqu1none fiofii ti 'iiiiifi iia-2%; was-dissolved n 1 0 1- 9 ex e id m v ee and l 2) When the firep aratiorideseribed in A (1) above long? were briigbledjlsimultaneoqsly z l two ours. e. 80 utlon was con'cen a e on errest;Lassen:tzssa iesriicze s eaters l a me diethylaminobutylamino)-p-benzoquirione obtained was The m a? "W ,sodmm sulflate n1 slighfl less than that obt-ainedin A (1) filtered, and petroleumcther was added to the-solut on, y y I r thereby precipitating l g. *of *2-(4-dietliylaminobuty1- amino)55-methylamino-p benzoquindne, a yellow solid B; Quaternary salts of -2 (4-dicthylaminobutylamino)- hi hmelt dai1-O3 106C a Y pbenzoquinone v a AnaIysis.'---Calculated: ,64.48%;H, 9.02%. .Found: 2-(4-diethylamino'butylaminoLfi benzoquinone was i' TQi%fj-. f quaternized -1by treatmcnt wit'haone molecular equivalent "B Quaternary T 4 4? "i ".?lf imt i m'm of methyl bromide to yield 2-(4-diethylaminobutylamino)- a5'"?hymn?!olplbenzoqumone I pnzoquinone m th r m 2-(4 diethylaminobutylamino) rs-nieflaylaminop-benioquinone reacts 'beri'z'ybclil'o'ride and with methyl 0 I u sulfate to yield, respectively, 2-(4-die'thylaminobu'tyli t amino)-5-methylamino-p-benzoquinone benzyl chloride,

NH-CHr-CHr-CHs-OHr-N-Gzfis which has the formula .B CH 0 r 2 5 I w 6Ov ,l SC S O Nneomcrn- -cnpcfir-N-cim '01 1211s CHPNH which melted at 146-148 C. 5

The amine reacts with benzyl chloride to yield 2-(4- 0 r. diethylamihobutylamiiro)-p-benzoqfiinone.benzy1 chloride, d 2; 4 i mi b f mi i 5 .h hy'1 fi benzoquinone methosulfate, which has the formula 33 V 34 7 I EXAMPLE 19 a i (a 50% excess) of N,N-diethyl-1,4-butanediamine;and oxygen was passed into the mixture while keeping the y y y -P- temperature of the mixture at 35-40 C. for about thirty benzoquinone and quaternary salts thereof hours. The solution was then concentrated and the resi- 0 due thus obtained was recrystallized from hot petroleum ether. There was obtained 4.5 g. of 2,5-bis-(4-diethylaminobutylamino) -p-benzoquinone, which melted at. 105- Analysis-Calculated: -N,.. 14.28%; C', 67.45%; H, 10.28%. Found: N, 14.12%; C, 67.69%; H, 10.41%.

B. Quaternary salts of 2,5 bis (4 diethylaminobutyl-v a rrzino)-p-b enzoquinone By substituting dimethylamine for the methylamine ema ployed in Example 18A, there is obtained as the product 2,5 bis (4 diethylaminobutylamino) p benzoof the reaction 2-(4-diethylaminobutylamino)-5-dimethylquinone was quaterniz'ed'with two equivalents of-methyl amino-p-benzoquinone, which reacts with allyl bromide bromide to yield 2,5 bis-(4-diethylarninobutylamino)-pand with methyl p-toluenesulfonate to yield, respectively, benzoquinone bis-methobromide,

2 (4 diethylaminobutylamino) 5 dimethylamino-pwhich melted at 229230 C. benzoquinone allyl bromide, which has the formula Analysis.--Calculated: N, 9.66%; Br, 27.55%.

0 Found: N, 9.31%; Br, 27.65%.

OHrCH=CH2 The amine reacted with two molecular equivalents of benzyl chloride to yield 2,5-bis-(4-diethylaminobutylammo)-p-benzoqumone bis-(benzyl chloride), having the (OH'hN can; structural formula and 2 (4 diethylaminobutylamino) 5 dimethylamino- CHPCa I NH-GHi-GHI-CHz-GHr-NC:Ha' i (kHz-43H: l I

1 CaHl C2HJ;NCH2-CH2-CH2 CH2NH CHHB $1 g p-benzoquinone methyl p-toluenesulfonate, which has 45 the formula 0 e e e which was a red, amorphous compound having an indefinite meltingpoint. NH-CHg-CHr-CHg-CHz-N-Cifls v Similarly, the amine reacts with ethyl chloride to yield 62H 2,5 a bis (4 diethylaminobutylamino) p benzoquinone (OHshN bis-ethochloride, having the structural formula aS-Cufli-CHKP) NH-CHr-CHr-CHrCHa- --C2Hs Ca 5\ 1\o H CaHs;N-CHt-QHfl-CH2-CHr-NH 02 $1 EXAMPLE 20 a i A. 2,5 bis (4 diethylaminobutylamino) p benzoquinone NH-om-cHP'cHz-om-Nwim To 8.3 g. of 2-(4-diethylaminobutylamino)-p-benzo- Interaction of the amine with two molecular equiva quinone in ml. of dioxane there was added 6.3 g. lents of p-cyanobenzyl bromide yields 2,5-bis-(4-diethyh EXAMPLE 21 A. 2,5 bis (5 diethylaminoamylamino) p benzquinane '36 to the reaction mixture. The red oil which precipitated solidified on standing to yield 2.5 g. of 2,5-bis-(-diethylun-cm-cm-on cm-N-c m 24 g. of N,N-diethyl-1,5-pentanediamine was added with cooling to g. of p-benzoquinone in 150 ml. of

i oant-le-om-(cnm-om-nn' aminoamylamino)-p-benzoquinone bis methobrornide,

having the formula which melted at'112l13 C.

Analysis.-Calculated: N, 9.18%; Found: N, 9.07%; Br, 25.68%.

The amine reacts with two molecular equivalents of &0 methyl p-toluene-sulfonate to yield 2,5-bis-(5-diethylaminoamylamino) p benzoquinone bis (methyl ptoluenesulfonate) EXAMPLE 22 A. 2,5 bis [5 (1 piperidyhamylaminojl p benzoquinone CHr-CHQ NH-CH C OH H OKs-OH; 'i D:- 0 a CHs-C 1 C 1 CH:(OH:)aOHz-NH GHQ-C weighed 4.9 g., was 2,5-bis-(S-diethylaminoamylamino)- p-benzoquinone. It melted at 94-98 C.

Analysis.Calculated: N, 13.32%. 12.96%.

Found: N,

g. of I-(S-aminoamyDpiperidine was added with cooling to a solution of 15 g. (an excess) of p-benzo- I quinone in 300 m1. of dioxane. The solution was warmed amino] -p-benzoquinone.

- 37 B. Quaternary salts of 2,5-bis-[5-(1-piperidyDamylaminol-p-benzaquinone 2,5 -bis- [5 1-piperidyl)amylamino] -p-benzoquinone reacts with two equivalents of methyl bromide, to yield 2,5- bis- [5-( l-piperidyl) amylamino] -p-benzoquinone bis-methobromide,

which melted at 26 1-270 0. (dec.)

"as B. Quaternary salts of 2-(Sflfthyltzm-inoamylamino)- I p-bengoquinone l OH: OHs-CH:

yl bromide to yield 2-(5-diethylaminoamylamino)-p-benzoquinone methobromide,

Analysis.Calculated: N, 8.83%; Br. 25.l9%., Foundg 9 cm 0 H N, 8.90%; Br, 25.25%. q The amine reacts with diethyl sulfate to yield 2,5-bis-[- NHCHr-(CHH)PCHI- l-piperidyl)amylaminol-p-benzoquinone bis-(ethosulr 0,191, fate), q

which had an indefinite melting point, ca. 113 C.

alls 0 GHQ-CHI NHC :-(CH:)aCHzN CH: OH2-C\g /C2 s OH 0% 0%, n om-(onm-cm nn I (so CHE-Cg sotclHs) Interaction of the amine with two molecular equivalents of p-methylbenzyl chloride yields 2,5-bis-[5-(1- piperidyDamylamino] -p-benzoquinone bis-(p-methylbenzyl chloride),

Analysis-Calculated: N, 7.79%; Br. 22.22%. Found! N, 7.57%; Br, 22.92%.

The amine reacts with one equivalent of benzyl chlo- EXAMPLE 23 A. Z-(S-diethylaminoamylamino)-p-benzoquinone (S-diethylaminoamylamino)-p-benzoquinone, which mclta ed at 84-86 C.

Analysis-Calculated: N, 10.60%. Found: N, 11.19%.

ride to yield Z-(S-diethylaminoamylamino)-p benioquinone benzyl chloride,

Interaction of the amine with p-trifluoromethylbenzyl v bromide yields 2-(5-diethylaminoamylamino)-p-benzoquinone p-trifiuoromethylbenzyl chloride,

9 v EXAMPLE 24 Th e amine reacts with allyl bromide to yield 2-[5-(1- A, 2-[5-(1.. 1 m piperidyl)amylaminol-p-benzoquinone allyl bromide O V I v V GHQ-CH, Q CH2-CH CH: -(CHDr-CIh-N n, H ore-on,

GH -CE, s-(CHa)z-CE,-N

Br Hr-CH:

Using a procedure similar to that described in Part A EXAMPLE A. 2,5-bis-(3-diethylaminopropylamino)-3,6-dichlor0- p-benzoquinone C! NH-CH:CHa-OHg-N(C1Hs):

(om),N-crrr-er1,-cn,-NH c1 l V y 0 of Example 8, p'-benzoquinone was reacted with one A solution of 7 g. of chloranil and 33 g. (an excess) of equivalent of l-(5-aminoamyl)piperidine. After concen- 25 N,N-diethyl-1,3-propanediamine in 100 ml. of dioxane trating the reaction mixture, there was obtained as a was heated on a steam bath for six hours and the reaction product 2-[5-( l-piperidyl)amylamino]-p-benzoquinone, mixture was then concentrated under reduced pressure. which melted at 176-177 C. The crystalline residue thus obtained was recrystallized Analysis.-Calculated: N, 10.14%; C, 69.53%; H, from hot ethanol to yield 7.2 g. of 2,5-bis-(3-diethylamii 8.75%. Found: N, 9.98%; C, 69.63%; H, 8.97%. nopropylamino)-3,6-dichloro-p-benzoquinone, in the form This amine reacts with hydrobromic acid to yield the of bronze-colored needles, which melted at 136-137 C. amine hydrobromide. Analysis.-Calculated: N, 12.93%; Cl, 16.36%.

Found: N, 12.92%; Ci, 15.92%.

Quaternary salts of 2'[5 (1-plperidyt)amylamm0]p- B. Quaternary salts of 2,5 bis- (3-diethylaminopr0pyl- 1 benzoqumone amino)-3,6-dichloro-p-bengoquinone When 2.- [5(l-p p yn ylaminol-p-ben20q11 0 5 g. of 2,5 bis (3 diethylaminopropylamino)-3,6- was quatel'fllfled y treatment W One q y l n 0f dichloro-p-benzoquinone was quaternized by heating with methyl .bromlder e e was-obta ned 2-[ S-(1-p1pendyD- 11 g. of benzyl chloridein 95% ethanol for six hours.

40 There was thus obtained 5.5 g. of 2,5-bis-(3-diethylaminopropylamino) 3,6 dichloro-p-benzoquinone bis-(benzyl chloride),

0 I CHz-CaHs Cl NH-CH CHkOH, flCHa--oHa-N C2155 l 02H: C:HaNCH:-CHs-CHr-NH C1 0135 C1 I 0 i amylaminol-p-benzoquiuone methobromide, which was a dark brown powder with an indefinite 0 melting point. I H CH3 g Analysis.Calcu1ated: N, 8.17%; Cl, 20.65%. Found: 1

NIH-CHr-(CHOa-Cflr-N CH: N, 8.22%; Cl, 20.60%.

Q, y In analogous fashion, the amine reacts with two mo- V lecular equivalents of benzyl bromide to yield 2,5-bis-(3- diethylaminopropylamino) 3,6-dichloro-p-benzoquinone bis-(benzyl bromide),

i CHr-CuHs Cl NHCH 0H CHPCH, :CH: C2116 Bl C1115 CzHs-N-CHa-CHr-CHa-NE 01 C211; Br

EXAMPLE 26 A. 2,5 bis [3 (I piperidyl)propylamino] 3,6 dibramo-p-benzoquinone and quaternary salts thereof i GHQ-CH2 Br NHCH:-CHz-CHz-N 0H, GHQ-CH5 OHz-CH: OH: N-GHr-OHg-CHQ-NH Br 

1. A COMPOUND SELECTED FROM THE GROUP OF QUATERNARY AMMONIUM COMPOUNDS HAVING THE FORMULAS 